Ilaria Maestrini1, Madjid Tagzirt1, Sophie Gautier1, Annabelle Dupont1, Anne-Marie Mendyk1, Sophie Susen1, Anne Tailleux1, Emmanuelle Vallez1, Bart Staels1, Charlotte Cordonnier1, Didier Leys1, Regis Bordet2. 1. From the Departments of Neurology (I.M., A.-M.M., C.C., D.L.) and Medical Pharmacology (S.G., R.B.), Degenerative and Vascular Cognitive Disorders, University Hospital CHU Lille, Inserm U1171, University of Lille, France; Department of Human Neurosciences (I.M.), "Sapienza" University of Rome, Italy; and European Genomic Institute for Diabetes (M.T., A.D., S.S., A.T., E.V., B.S.), University Hospital CHU Lille, Inserm U1011, Institut Pasteur of Lille, University of Lille, France. 2. From the Departments of Neurology (I.M., A.-M.M., C.C., D.L.) and Medical Pharmacology (S.G., R.B.), Degenerative and Vascular Cognitive Disorders, University Hospital CHU Lille, Inserm U1171, University of Lille, France; Department of Human Neurosciences (I.M.), "Sapienza" University of Rome, Italy; and European Genomic Institute for Diabetes (M.T., A.D., S.S., A.T., E.V., B.S.), University Hospital CHU Lille, Inserm U1011, Institut Pasteur of Lille, University of Lille, France. regis.bordet@chru-lille.fr.
Abstract
OBJECTIVE: In acute cerebral ischemia, circulating neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are positively associated with stroke severity and worse outcomes. Mediators of this effect are unknown. We aimed to investigate (1) the relationship between plasma matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) concentrations with stroke severity and outcome and (2) MMP-9 and MPO release after ex vivo stimulation of neutrophils by recombinant tissue plasminogen activator (rtPA). METHODS: We analyzed data collected in 255 patients with supratentorial cerebral infarcts recruited within 48 hours of symptoms onset irrespective of rtPA treatment. The endpoints were excellent outcome (modified Rankin Scale score 0-1), symptomatic intracerebral hemorrhage (European Cooperative Acute Stroke Study-II definition), and death at 3 months. The role of rtPA treatment on peripheral neutrophil degranulation was investigated in 18 patients within 4.5 hours and after 72 hours. RESULTS: Neutrophil counts, NLR, and MPO plasma concentrations, but not MMP-9, were positively correlated with stroke severity. Higher neutrophil counts and NLR were independently associated with worse outcomes and higher mortality rates at month 3. Higher MPO plasma concentrations, but not MMP-9, were associated with worse outcome. Neutrophil-derived MMP-9, after ex vivo rtPA stimulation, but not MPO, were higher after 72 hours in patients treated by IV rtPA but not associated with hemorrhagic transformation. CONCLUSIONS: Neutrophil counts, NLR, and MPO plasma concentrations are associated with worse outcome in patients with acute cerebral ischemia, in contrast to MMP-9. Further investigations are needed to deepen our knowledge on MPO's role in the deleterious effect of neutrophils because it could represent a potential therapeutic target.
OBJECTIVE: In acute cerebral ischemia, circulating neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are positively associated with stroke severity and worse outcomes. Mediators of this effect are unknown. We aimed to investigate (1) the relationship between plasma matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) concentrations with stroke severity and outcome and (2) MMP-9 and MPO release after ex vivo stimulation of neutrophils by recombinant tissue plasminogen activator (rtPA). METHODS: We analyzed data collected in 255 patients with supratentorial cerebral infarcts recruited within 48 hours of symptoms onset irrespective of rtPA treatment. The endpoints were excellent outcome (modified Rankin Scale score 0-1), symptomatic intracerebral hemorrhage (European Cooperative Acute Stroke Study-II definition), and death at 3 months. The role of rtPA treatment on peripheral neutrophil degranulation was investigated in 18 patients within 4.5 hours and after 72 hours. RESULTS: Neutrophil counts, NLR, and MPO plasma concentrations, but not MMP-9, were positively correlated with stroke severity. Higher neutrophil counts and NLR were independently associated with worse outcomes and higher mortality rates at month 3. Higher MPO plasma concentrations, but not MMP-9, were associated with worse outcome. Neutrophil-derived MMP-9, after ex vivo rtPA stimulation, but not MPO, were higher after 72 hours in patients treated by IV rtPA but not associated with hemorrhagic transformation. CONCLUSIONS: Neutrophil counts, NLR, and MPO plasma concentrations are associated with worse outcome in patients with acute cerebral ischemia, in contrast to MMP-9. Further investigations are needed to deepen our knowledge on MPO's role in the deleterious effect of neutrophils because it could represent a potential therapeutic target.
Authors: Sara Bernardo-Castro; João André Sousa; Ana Brás; Carla Cecília; Bruno Rodrigues; Luciano Almendra; Cristina Machado; Gustavo Santo; Fernando Silva; Lino Ferreira; Isabel Santana; João Sargento-Freitas Journal: Front Neurol Date: 2020-12-09 Impact factor: 4.003